Association of EEG Response to Hypertonic Saline and Neurologic Outcomes in Pediatric Acute Brain Injury

Association of EEG Response to Hypertonic Saline and Neurologic Outcomes in Pediatric Acute Brain Injury | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association of EEG Response to Hypertonic Saline and Neurologic Outcomes in Pediatric Acute Brain Injury Emma L Mazzio, Eva Catenaccio, Raymond Liu, Arastoo Vossough, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7200528/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Jan, 2026 Read the published version in Neurocritical Care → Version 1 posted 5 You are reading this latest preprint version Abstract Background EEG is a critical tool for neuromonitoring and neuroprognostication in children with acute brain injury. Quantitative EEG (qEEG), particularly the alpha-delta ratio (ADR), can detect worsening cerebral ischemia in adults, but it is unknown whether it can identify more subtle and transient changes in cerebral blood flow, such as those induced by hypertonic saline (HTS), in children. We aimed to determine whether we could identify a cohort of patients with an ADR response to HTS and to evaluate the association between an ADR response and neurologic outcomes in critically ill children with acute brain injury. Methods We conducted a retrospective cohort study of patients admitted to a pediatric intensive care unit with acute brain injury who received HTS during EEG monitoring from 2018–2023. The ADR was calculated before and after HTS administration. An ADR response was defined as > 20% increase from baseline within 30 minutes of receiving HTS in either hemisphere. The primary outcome was survival with favorable neurologic outcome, defined as a Functional Status Scale (FSS) change < 3 from pre-hospital baseline to discharge. Secondary outcome was survival to hospital discharge. Results Among 87 patients (median age 10 years [IQR 3.6–14.5], 46% female), 28% (24/87) had an ADR response to HTS. ADR responders were older (12.9 vs. 8.0 years, p = 0.004) and more likely to have continuous, normal-voltage EEG backgrounds (67% vs. 40%, p = 0.006). Patients with an ADR response had 4 times increased odds of favorable outcome and survival (OR 4.0, 95% CI 1.3–12.7; OR 3.9, 95% CI 1.0–10.7, respectively). Conclusions An ADR increase > 20% following HTS was associated with increased odds of survival with favorable neurologic outcome and survival to hospital discharge in critically ill pediatric patients with acute brain injury. qEEG response to HTS may serve as a real-time, noninvasive biomarker of cerebral perfusion responsiveness. Pediatrics Brain Injuries Critical Care Quantitative EEG Cerebral Blood Flow Hypertonic Saline Prognosis Introduction Acute brain injury accounts for 15% of pediatric intensive care units (PICUs) admissions and is a leading cause of morbidity and mortality. 1 – 4 The acutely injured brain is highly vulnerable to secondary insults such as cerebral edema, elevated intracranial pressure, and impaired cerebral blood flow, all of which can exacerbate injury and worsen outcomes. Patients with acute brain injury frequently undergo continuous electroencephalographic (EEG) monitoring to detect and guide management of subclinical seizures. 5 – 8 Additionally, EEG background features are biomarkers of acute brain injury severity. More normal background features such as continuous activity, the presence of faster frequencies, and the presence of variability are associated with favorable neurologic outcomes. 9 – 16 Further, tracking the trajectory of a patient’s EEG background over the course of an illness can provide insight into the severity of the disease process, response to therapies, and inform prognosis. 17 , 18 Quantitative EEG (qEEG) allows for objective assessment of EEG background activity by deconstructing raw EEG signals into frequency bands (alpha, beta, theta, and delta) and calculating the power within each frequency band over time. qEEG metrics have been associated with both cerebral injury severity and neurologic outcomes in pediatric populations. 19 – 22 The alpha-delta ratio (ADR), a commonly used qEEG metric in adult neurocritical care, reflects the relative balance of faster (alpha) and slower (delta) frequency components. Cerebral blood flow is one of many factors that modulates ADR; reductions in cerebral blood flow lead to a loss of faster frequencies and a predominance of slower waveforms, yielding a decreased ADR. 23 – 26 In critically ill adults, ADR is sensitive to clinically apparent ischemic events such as delayed cerebral ischemia following subarachnoid hemorrhage. 21 , 27 – 38 Hypertonic saline (HTS) is commonly administered to patients to manage intracranial hypertension, potentially improving cerebral blood flow through osmotic shifts, reduction in blood viscosity, and plasma volume expansion. 39 – 41 It is unclear whether changes in ADR are demonstrable after more subtle and transient increases in cerebral blood flow, such as those induced by HTS. Furthermore, it is unknown whether transient increases in ADR have prognostic significance in children with acute brain injury. Thus, in a cohort of children with acute brain injury, we aimed to determine whether administration of clinically indicated 3% HTS was associated with an increase in ADR, and whether there was an association between ADR response to HTS and favorable neurologic outcome. We hypothesized that patients with an ADR response to HTS would have higher rates of survival with favorable neurologic outcome compared to patients without an ADR response. Lastly, we evaluated the relationship between a sustained versus a transient ADR response to HTS and outcome, hypothesizing that patients with a sustained ADR response would have an increased likelihood of survival with a favorable neurologic outcome. Methods This was a single-center retrospective observational cohort study of patients admitted to the PICU with an acute brain injury who received at least one dose of HTS as part of clinical care while undergoing continuous electroencephalographic (cEEG) monitoring from January 1, 2018, to July 31, 2023. Exclusion criteria included: (1) younger than three months of age, (2) excessive artifact, as determined by an epileptologist, rendering it unsuitable for quantitative analysis, and (3) insufficient EEG data surrounding the analyzed HTS dose. The study was approved by the Children’s Hospital of Philadelphia Institutional Review Board, and a waiver of consent was obtained for this retrospective review of clinically collected data. We obtained clinical characteristics, including pre-ICU admission baseline and hospital discharge Functional Status Scale (FSS) scores from a local Virtual Pediatric Systems (VPS) database. 42 We abstracted the timing and dose of hypertonic saline (HTS), along with pre- and post-administration sodium and carbon dioxide (CO₂) values, from the electronic medical record. Pre-HTS values were defined as the sodium and CO₂ measurements obtained within 3 hours prior to HTS administration, selecting the value closest to the time of administration. Post-HTS values were the most proximal measurements within 3 hours after administration. CO₂ levels were preferentially obtained from arterial or venous blood gases. If unavailable, we used hourly recorded end-tidal CO₂ values. For each patient, only the first dose of 3% HTS administered during continuous EEG monitoring was included in the analysis. At our institution, 3% HTS was administered at a standard dose of 2–5 mL/kg, and no other concentrations were used. Patients may have received a dose of HTS prior to cEEG monitoring or had insufficient EEG data surrounding a prior dose for analysis (e.g., EEG disconnected to obtain neuroimaging). Neuroimaging studies were independently reviewed by a pediatric neuroradiologist, and the severity of acute brain injury was categorized as normal (no acute injury), moderate (injury not meeting severe criteria), or severe (presence of midline shift or herniation). cEEG was performed as part of clinical care using a standard 10–20 electrode montage for all patients (Natus, version 9.3.1 2013). A board certified pediatric electroencephalographer reviewed all raw EEG tracings to ensure the segments surrounding HTS doses were free of artifact that could impact qEEG analysis and that no seizures were present. Additionally, they classified the cEEG background into three categories based on standard definitions: (1) continuous with normal voltage, (2) continuous or nearly continuous with low or normal voltage, and (3) discontinuous, burst-suppression, or suppressed patterns. 43 Raw EEG signals were processed in Persyst (Version 15, Persyst Development Corporation, Prescott, AZ), utilizing artifact reduction and fast Fourier transformation (FFT) analysis to compute power spectral densities estimates. Alpha (8–13 Hz) and delta (1–4 Hz) power were extracted using a running average over 8-second epochs. The ADR for each hemisphere was calculated as the quotient of alpha power divided by delta power. We abstracted the ADR for a total of 40 minutes, extending from 5 minutes prior to the HTS dose to 30 minutes following the 5-minute infusion duration. Baseline ADR was the average ADR over the 5-minute period before HTS administration. Post-HTS ADR was calculated as the average ADR during each of the following time intervals: 0–10, 11–20, and 21–30 minutes following HTS administration. ADRs were calculated separately for each hemisphere for all timepoints. An ADR response to HTS was defined as an increase of greater than 20% from baseline in either hemisphere during at least one of the three post-HTS time intervals. The 20% threshold was extrapolated from prior studies using ADR to detect delayed cerebral ischemia in adult subarachnoid hemorrhage, hemispheric differences in stroke, and cerebral blood flow changes during neonatal aortic arch reconstruction. 28 , 29 , 32 , 34 – 36 , 38 Among patients with an ADR response, the response was categorized as sustained or transient. A sustained response was defined as an ADR increase of > 20% that persisted for at least two consecutive time intervals (totaling at least 20 minutes) or from onset through the end of the 30-minute post-HTS monitoring interval; all other responses were classified as transient responders . The primary outcome was survival with a favorable neurologic outcome, defined as survival with an FSS score change of < 3 from pre-ICU admission to hospital discharge. 44 The secondary outcome was survival to hospital discharge. We report descriptive statistics as median and interquartile ranges (IQR) for continuous variables and frequencies with percentages for categorical variables. We used Chi-squared or Fisher exact tests to examine associations between categorical variables and outcome, and Wilcoxon rank-sum to compare continuous variables between exposure and outcome groups. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. Univariable logistic regression was used to assess the association between ADR response and outcome. As a secondary analysis we stratified patients based on EEG background category to assess if the association between ADR response and outcome differed by EEG background. We conducted two sensitivity analyses to exclude patients who (1) received a dose of HTS prior to cEEG initiation, and (2) had acute hypoxic-ischemic brain injury. Results Among 151 patients who met inclusion criteria, 64 were excluded due to age less than 3 months (n=4), excessive EEG artifact (n=7), or insufficient EEG data (n=53). Thus, 87 patients were analyzed. The median age was 10.4 years (IQR 3.6–14.5), and 46% were female. An ADR response to HTS occurred in 28% of patients (24/87). Compared to ADR non-responders, ADR responders were older (12.9 [10.5-15.0] vs. 8.0 [2.2-12.2] years, p = 0.004), but the two groups did not differ in other demographics or illness severity metrics (Table 1). ADR responders were more likely to have a continuous and normal voltage EEG background compared to ADR non-responders (67% vs. 40%, p = 0.01). Median dose of HTS was similar between responders and non-responders (5.0 [4.3-5.0] vs. [4.6 3.0-5.0] mL/kg, p=0.28). Changes in serum sodium and CO 2 levels pre- and post-HTS dose were similar between ADR responder groups (Table 1). Survival with a favorable neurologic outcome occurred in 17% of patients (15/87), and survival to hospital discharge occurred in 66% of patients (58/87) (Tables 2 and 3). More ADR responders survived with a favorable neurologic outcome than ADR non-responders (33% vs. 11%, p=0.03). Having an ADR response was associated with 4 times increased odds of favorable neurologic outcome (OR 4.0, 95% CI 1.3–12.7). Survival to hospital discharge was higher among ADR responders compared to non-responders (83% vs. 60%, p=0.05), corresponding to 3.9 times greater odds of survival (OR 3.9, 95% CI 1.0–10.7) Among ADR responders, 25% (6/24) patients demonstrated a response onset within the 0–10 minute interval, 66% (16/24) during the 11–20 minute interval, and 8% (2/24) during the 21–30 minute interval. The ADR response was sustained in 75% (18/24) patients and transient in 25% (6/24) patients. Among patients who survived with a favorable neurologic outcome, a greater proportion had a sustained versus transient ADR response, although the difference was not statistically significant (39% vs. 17%, OR 3.2 [0.3 – 33.6]). When stratified by EEG background category, the association between ADR response and favorable neurologic outcome remained directionally consistent but was not statistically significant across strata (Table 4). In patients with continuous and normal voltage EEG, survival with favorable neurologic outcome occurred in 44% of ADR-responders compared to 28% of ADR non-responders (OR 2.0 [0.5-7.7). No patients with severely abnormal EEG backgrounds survived with favorable neurologic outcome. Forty-two percent (37/87) of patients received at least one dose of HTS prior to cEEG initiation. When evaluating the 50 patients whose first dose of HTS administrations was captured on cEEG, ADR responders had higher rates of survival with favorable neurologic outcomes than ADR non-responders (38% vs. 8%, OR 7.08 [1.39–35.99]). When evaluating patients without hypoxic ischemic brain injury (n=63), there was no difference in rates of favorable neurologic outcome (44% vs. 17%, OR 2.5 [0.7–8.4]) or survival to hospital discharge (90% vs. 71%, OR 3.8 [0.76–18.9) among ADR responders and ADR non-responders. Discussion In a cohort of critically ill children with acute brain injury, patients with a >20% increase in ADR within 30 mins of HTS administration had four times the odds of survival with a favorable neurologic outcome compared to ADR non-responders. The association between an ADR response and favorable neurologic outcome was strongest among patients with more normal EEG backgrounds (continuous and normal voltage), highlighting a subgroup with likely less severe injury in whom a response to HTS may more readily translate into clinical benefit. most clinically relevant. An increase in faster EEG frequencies (alpha) or a reduction in slower frequencies (delta) following HTS administration likely reflects improved cerebral blood flow in salvageable brain tissue. 21,26–28 Thus, an ADR response to HTS may potentially serve as a noninvasive biomarker of neurovascular responsiveness in acute brain injury, identifying patients with the potential to benefit from strategies that improve cerebral blood flow. ADR can be calculated automatically in real-time and displayed continuously at the bedside, allowing clinicians to evaluate EEG changes in response to interventions aimed at improving cerebral physiology. The qEEG response, or lack of response, to an intervention may provide information about the physiologic state of the brain that can guide subsequent neuroprotective therapies. For example, the presence of an ADR response to HTS may suggest further therapies aimed at improving cerebral blood flow could be beneficial. On the other hand, the absence of an ADR response may identify children with less severe brain injury and intact cerebral autoregulation, children for whom a single dose of HTS is insufficient and more aggressive ICP management is needed, or children with severe irreversible brain injury unlikely to benefit from therapies aimed at increasing cerebral perfusion. While qEEG and serial ADR monitoring are commonly used in adult neurocritical care and have demonstrated high sensitivity (83–100%) and specificity (74–84%) for detecting delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage, 29,35,37 , it is an emerging tool for neuromonitoring in pediatric populations. 20,22,27,30,31 For example, in neonates undergoing congenital heart surgery, the development of an interhemispheric alpha-delta ratio (ADR) difference greater than 25% has been associated with subsequent neurologic injury. 27,28 Our findings build on prior work by demonstrating the value of a detectable, real-time qEEG response to a physiologic intervention. Identifying patients with an ADR response following HTS may help understand the cerebral physiological and likelihood of clinical benefit from additional hyperosmolar therapy. There is mixed evidence and large practice variation in the use of HTS in patients with primarily cytotoxic cerebral edema from etiologies such as hypoxic ischemic brain injury from cardiac arrest, infectious encephalitis, and ischemic strokes. The use of HTS in hypoxic ischemia brain injury decreases brain edema in animal models but has failed to show improvement in clinical studies. 45,46 However, recent work suggests that in hypoxic ischemic brain injury, HTS may reduce perivascular edema and thereby improve oxygen diffusion into brain tissue. 47 In our cohort, only one of the 24 patients with hypoxic ischemic brain injury achieved a favorable outcome, and this patient was an ADR responder. In this context, an EEG-based marker like ADR responsiveness may offer a physiologic tool to differentiate patients likely to benefit from HTS from those who may require alternative neuroprotective management strategies. EEG background following pediatric acute brain injury is a strong predictor of outcome. 5,9–11,48 In our study, nearly all children who survived with favorable neurologic outcome exhibited continuous and normal voltage EEG backgrounds. Although not statistically significant, the presence of an ADR response appeared to further stratify patients with continuous EEG backgrounds, with double the percentage of patients experiencing favorable outcomes who had both a continuous EEG background and an ADR response to HTS compared to patients with a continuous EEG background who did not have an ADR response to HTS. These findings warrant further investigation in larger cohorts. Among patients with continuous, normal-voltage EEGs who did not demonstrate an ADR response, it is possible that some had relatively mild injuries with preserved cerebral autoregulation such that HTS did not produce a sufficient increase in cerebral blood flow to elicit detectable EEG changes. Others may have received HTS in the setting of a clinical concern despite the patient not having intracranial hypertension, in which case a marked change in cerebral blood flow would not be expected. Notably, only one patient with a severely abnormal EEG background in our cohort exhibited an ADR response, and this patient did not survive to hospital discharge. Taken together, these findings suggest that ADR response should not be used in isolation to predict neurologic outcome and that larger studies are needed to better define the relationship between ADR response and EEG background features. Our study has several limitations. The retrospective, single‑center design and modest sample size limited our ability to perform multivariable regression analyses. Our cohort was comprised of patients who received HTS doses while on EEG, often using a patient’s second or third dose for analyses, potentially underestimating the observed association, as the efficacy of HTS may wane with repeated doses. As this was a retrospective observational study, we could not account for the effect a prior HTS response had on the clinician’s decisions to give additional HTS. EEG background categorization was based on a five-minute epoch immediately preceding HTS administration. While this short interval was chosen to capture the acute cerebral physiology at the time clinicians made the decision to give HTS, it risks potential misclassification of a patient’s true baseline ADR that may have been more evident if a longer baseline interval was used. We did not have concurrent intracranial pressure data to determine whether HTS-associated ADR changes were associated with a decrease in intracranial pressure or an increase in cerebral perfusion pressure. Finally, the 20% ADR threshold was extrapolated from prior studies of cerebral ischemia in adults and children, but prospective studies are needed to determine optimal cut‑points in children. 28,29,32,34–36,38 Conclusion A greater than 20% increase in ADR within 30 minutes of HTS administration was associated with increased survival with favorable neurologic outcome in critically ill children with acute brain injury. Quantitative EEG response to physiologic-targeted interventions is a promising noninvasive tool to aid in both prognostication and therapeutic decision-making in pediatric acute brain injury. Declarations We confirm that this manuscript complies with all author instructions provided. Author Contributions Emma L. Mazzio MD: Conceptualization, Methodology, Investigation, Formal analysis, Writing - original draft, Writing - review & editing Eva Catenaccio MD: Conceptualization, Methodology, Investigation, Writing - review & editing Raymond Liu MD: Conceptualization, Investigation, Formal analysis, Writing - review & editing Arastoo Vossough MD PhD: Investigation, Writing - review & editing Nicholas S. Abend MD MSCE: Conceptualization, Investigation, Writing - review & editing Alicia M Alcamo MD MPH: Conceptualization, Writing - review & editing Jimmy Huh MD: Conceptualization, Writing - review & editing Shih-shan Chen MD: Conceptualization, Writing - review & editing Robert A Berg MD: Conceptualization, Methodology, Investigation, Writing - review & editing, Supervision Alexis A Topjian MD MSCE: Methodology, Formal analysis, Writing - original draft, Writing- review & editing, Supervision Craig Press MD PhD: Conceptualization, Investigation, Methodology, Writing - review & editing, Supervision Matthew P Kirschen MD PhD: Conceptualization, Methodology, Formal analysis, Writing - review & editing, Supervision We confirm that all authorship requirements have been met and the final manuscript has been approved by all authors. This manuscript has not been published elsewhere and is not under consideration by another journal. The study was approved by the Children’s Hospital of Philadelphia Institutional Review Board, and waiver of consent was obtained for this retrospective review of clinically collected data. A.A.T. receives NIH funding to her institution and serves as an Associate Editor for Resuscitation (Elsevier). A.M.A. receives research funding from Edwards Lifesciences for work unrelated to this project. M.P.K. receives NIH funding to his institution (NINDS K23NS116120). Persyst provided a complimentary research license (version 15) for this project. No other authors have conflicts of interest to disclose. We used the Strobe reporting checklist, attached. No funding sources for this study. References Au AK, Carcillo JA, Clark RSB, Bell MJ. Brain injuries and neurological system failure are the most common proximate causes of death in children admitted to a pediatric intensive care unit. 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Continuous EEG Monitoring for Early Detection of Delayed Cerebral Ischemia in Subarachnoid Hemorrhage: A Pilot Study. Neurocrit Care . 2016;24(2):207-216. doi:10.1007/s12028-015-0205-y Claassen J, Hirsch LJ, Kreiter KT, et al. Quantitative continuous EEG for detecting delayed cerebral ischemia in patients with poor-grade subarachnoid hemorrhage. Clin Neurophysiol . 2004;115(12):2699-2710. doi:10.1016/j.clinph.2004.06.017 Wickering E, Gaspard N, Zafar S, et al. Automation of Classical QEEG Trending Methods for Early Detection of Delayed Cerebral Ischemia: More Work to Do. J Clin Neurophysiol . 2016;33(3):227. doi:10.1097/WNP.0000000000000278 Scherschinski L, Catapano JS, Karahalios K, et al. Electroencephalography for detection of vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a retrospective analysis and systematic review. Published online March 1, 2022. doi:10.3171/2021.12.FOCUS21656 Kamitaki BK, Tu B, Wong S, Mendiratta A, Choi H. Quantitative EEG Changes Correlate With Post-Clamp Ischemia During Carotid Endarterectomy. J Clin Neurophysiol . 2021;38(3):213-220. doi:10.1097/WNP.0000000000000686 Qureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med . 2000;28(9):3301-3313. doi:10.1097/00003246-200009000-00032 Suarez JI. Hypertonic saline for cerebral edema and elevated intracranial pressure. Cleve Clin J Med . 2004;71 Suppl 1:S9-13. doi:10.3949/ccjm.71.suppl_1.s9 Tseng MY, Al-Rawi PG, Pickard JD, Rasulo FA, Kirkpatrick PJ. Effect of hypertonic saline on cerebral blood flow in poor-grade patients with subarachnoid hemorrhage. Stroke . 2003;34(6):1389-1396. doi:10.1161/01.STR.0000071526.45277.44 Virtual Pediatric Systems | Online. Accessed June 18, 2025. https://myvps.org/ Hirsch LJ, Fong MWK, Leitinger M, et al. American Clinical Neurophysiology Society’s Standardized Critical Care EEG Terminology: 2021 Version. J Clin Neurophysiol . 2021;38(1):1-29. doi:10.1097/WNP.0000000000000806 Pollack MM, Holubkov R, Glass P, et al. Functional Status Scale: new pediatric outcome measure. Pediatrics . 2009;124(1):e18-28. doi:10.1542/peds.2008-1987 Fuller ZL, Faro JW, Callaway CW, Coppler PJ, Elmer J. Recovery among post-arrest patients with mild-to-moderate cerebral edema. Resuscitation . 2021;162:149-153. doi:10.1016/j.resuscitation.2021.02.033 Marasini S, Jia X. Neuroprotective Approaches for Brain Injury After Cardiac Arrest: Current Trends and Prospective Avenues. J Stroke . 2024;26(2):203-230. doi:10.5853/jos.2023.04329 Hoiland RL, Ainslie PN, Wellington CL, et al. Brain Hypoxia Is Associated With Neuroglial Injury in Humans Post-Cardiac Arrest. Circ Res . 2021;129(5):583-597. doi:10.1161/CIRCRESAHA.121.319157 Admiraal MM, Horn J, Hofmeijer J, et al. EEG reactivity testing for prediction of good outcome in patients after cardiac arrest. Neurology . 2020;95(6):e653-e661. doi:10.1212/WNL.0000000000009991 Tables Table 1. Patient Demographic and Clinical Characteristics by ADR Response to Hypertonic Saline All Patients (n=87) ADR Responder (n=24) ADR Non-Responder (n=63) p value Age (years) (median [IQR]) 10.4 [3.6-14.5] 12.9 [10.6-15.0] 8.0 [2.2-12.2] 0.004 Female Male 40 (46%) 47 (54%) 15 (63%) 9 (38%) 25 (40%) 38 (60%) 0.09 Pre-ICU FSS 6 [6-6] 6 [6-6] 6 [6-6] 0.82 PRISM3 Score 11 [5-17] 11 [5-15] 11 [6-18] 0.55 Previously healthy 57 (66%) 18 (75%) 39 (62%) 0.37 Etiology of Acute Brain Injury Anoxic Trauma ICH non-traumatic Neuroinflammatory/infectious Metabolic Ischemic stroke Status epilepticus Other 24 (28%) 24 (28%) 15 (17%) 12 (14%) 4 (6%) 4 (6%) 2 (2%) 2 (2%) 3 (13%) 9 (38%) 5 (38%) 3 (13%) 2 (8%) 0 (0%) 2 (8%) 0 (0%) 21 (33%) 15 (24%) 10 (16%) 9 (14%) 2 (3%) 4 (6%) 0 (0%) 2 (3%) 0.08 EEG background category Cont, normal voltage Cont./nearly cont. +/- low voltage Discont./ Suppressed/ Burst-suppression 41 (47%) 23 (26%) 23 (26%) 16 (67%) 7 (29%) 1 (4%) 25 (40%) 32 (51%) 6 (10%) 0.006 Neuroimaging severity (n=81) Normal Mild to Moderate Severe 9 (10%) 46 (53%) 25 (29%) 2 (8%) 17 (71%) 5 (21%) 7 (11%) 30 (46%) 20 (32%) 0.35 Dose of HTS (ml/kg) 4.8 [3.1-5.0] 5.0 [4.3-5.0] 4.6 [3.0-5.0] 0.28 Pre-HTS Sodium (n= 85) ∆ Sodium (n = 84) Pre-HTS CO2 (n= 85) ∆ CO2 (n = 85) 139 [135-145] 2 [1-4] 36 [33-39] 0 [-2 -2] 142 [139-145] 2 [1-4] 35 [31-38] 1 [-3-2] 138 [134-145] 2 [1-4] 36 [33-40] 0 [-2-2] 0.06 0.75 0.14 0.81 FSS = Functional Status Score, PRISM3 = Pediatric risk of Mortality Score 3, Cont. = continuous, Discont. = discontinuous, ICH = intracranial hemorrhage, HTS= hypertonic saline, ∆ Sodium = Pre/post HTS change, CO2 = carbon dioxide level from blood gas, ∆ CO2 = Pre/post HTS change in CO2 from blood gas or EtCO2. Table 2: Association Between ADR Response to HTS and Favorable Neurologic Outcome All Patients (n=87) ADR Responder (n=24) ADR Non-Responder (n=63) p value Odds Ratio (95% CI) Favorable Neurologic Outcome 15 (17%) 8 (33%) 7 (11%) 0.03 4.0 (1.3-12.7) Survival 58 (66%) 20 (83%) 38 (60%) 0.05 3.9 (1.0-10.7) Table 2: Association between ADR response and favorable neurologic outcome and survival to hospital discharge. (ADR = alpha-delta ratio) Table 3: Patient Demographic and Clinical Characteristics by Primary Outcome Favorable Neuro Outcome (n=15) Non-Favorable Neuro Outcome (n=72) p value Age (years) (median [IQR]) 10.4 [6.9-13.9] 10.4 [2.8-14.5] 0.32 Female Male 9 (60%) 6 (40%) 31 (43%) 41 (57%) 0.36 Baseline FSS 6 [6-6] 6 [6-6] 0.29 PRISM3 Score 5 [5-15] 13 [8-18] 0.001 Previously healthy 8 (53%) 49 (68%) 0.37 Etiology of Acute Brain Injury Hypoxic Ischemic Trauma ICH non-traumatic Neuroinflammatory/infectious Metabolic Ischemic stroke Status epilepticus Other 1 (7%) 2 (13%) 4 (27%) 4 (27%) 3 (20%) 0 (0%) 1 (7%) 0 (0%) 23 (32%) 22 (30%) 11 (15%) 8 (11%) 1 (1%) 4 (6%) 1 (1%) 2 (3%) 0.01 EEG background category Cont. normal voltage Cont./nearly cont. +/- low voltage Discont./suppressed/ Burst-suppression 14 (93%) 1 (7%) 0 (0%) 27 (38%) 22 (31%) 23 (32%) <0.001 Neuroimaging severity Normal Mild to Moderate Severe 3 (20%) 10 (67%) 2 (13%) 6 (8%) 37 (51%) 23 (32%) 0.16 FSS = Functional Status Score, PRISM3 = Pediatric risk of Mortality Score 3, Cont. = continuous, Discont. = discontinuous, ICH = intracranial hemorrhage, HTS= hypertonic saline. Table 4: Association Between ADR Response to HTS and Outcome, Stratified by EEG Background Continuous, Normal Voltage Background EEG All (n=41) ADR Responder (n =16) ADR Non-Responder (n=25) p value OR Favorable Neurologic Outcome 14 (34%) 7 (44%) 7 (28%) 0.48 2.0 [0.5-7.7] Survival 35 (85%) 15 (93%) 20 (80%) 0.36 3.3 [0.4- 94.8] Continuous or Nearly Continuous +/- Low Voltage All (n=23) ADR Responder (n=7) ADR Non-Responder (n=16) p value OR Favorable Neurologic Outcome 1 (4%) 1 (14%) 0 (0%) 0.30 - Survival 15 (65%) 5 (71%) 10 (62%) 1.00 1.4 [0.21- 13.98] Discontinuous, Suppressed, Burst suppressed All (n=23) ADR Responder (n=1) ADR Non-Responder (n=22) p value OR Favorable Neurologic Outcome 0 0 0 - - Survival 8 (34%) 0 8 1.00 - Table 4: Comparison of favorable neurologic outcome and survival to hospital discharge among patients with and without an ADR response to hypertonic saline, stratified by EEG background category. (ADR = alpha-delta ratio; EEG = electroencephalography) Supplementary Files STROBEchecklistMazzioHTSEEG.docx Cite Share Download PDF Status: Published Journal Publication published 08 Jan, 2026 Read the published version in Neurocritical Care → Version 1 posted Reviewers agreed at journal 28 Jul, 2025 Reviewers invited by journal 28 Jul, 2025 Editor invited by journal 28 Jul, 2025 Editor assigned by journal 25 Jul, 2025 First submitted to journal 24 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7200528","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":492075912,"identity":"7429798d-dfd3-4bdd-83b2-6e6dfc74e0b2","order_by":0,"name":"Emma L Mazzio","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAt0lEQVRIiWNgGAWjYLCCBAYGOQYJMJOZeC3GJGoBgsQGorXoth9//OFBhU16/+zmYw8YKqwTGwhpMTuTkGCQcCYtd8adY+kGDGfSidByIOFAQmLb4dwNEjlmEoxth4nQcv5hw4HEtv/pBmAt/4jRciOZsSGx7UACREsDUVqeMTMknEk2nHEjLd0g4Vi6MREOS3/88UeFnTz/jORjDz7UWMsS1IIM2EBxShpgI1XDKBgFo2AUjBAAAGzjQI2gy9tiAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0009-0003-0143-330X","institution":"CHOP: The Children's Hospital of Philadelphia","correspondingAuthor":true,"prefix":"","firstName":"Emma","middleName":"L","lastName":"Mazzio","suffix":""},{"id":492075913,"identity":"8dcb52e2-4000-4105-92cc-eb278d5b7e70","order_by":1,"name":"Eva Catenaccio","email":"","orcid":"","institution":"CHOP: The Children's Hospital of Philadelphia","correspondingAuthor":false,"prefix":"","firstName":"Eva","middleName":"","lastName":"Catenaccio","suffix":""},{"id":492075914,"identity":"7181c462-c9da-429f-8a2d-edab135e9e62","order_by":2,"name":"Raymond Liu","email":"","orcid":"","institution":"CHOP: The Children's Hospital of Philadelphia","correspondingAuthor":false,"prefix":"","firstName":"Raymond","middleName":"","lastName":"Liu","suffix":""},{"id":492075915,"identity":"a447aedb-c0e1-44ec-b167-cff70d2656be","order_by":3,"name":"Arastoo Vossough","email":"","orcid":"","institution":"CHOP: The Children's Hospital of Philadelphia","correspondingAuthor":false,"prefix":"","firstName":"Arastoo","middleName":"","lastName":"Vossough","suffix":""},{"id":492075916,"identity":"87cabfbb-0d88-4e47-8c9a-3d2639596a0c","order_by":4,"name":"Nicholas S Abend","email":"","orcid":"","institution":"CHOP: The Children's Hospital of Philadelphia","correspondingAuthor":false,"prefix":"","firstName":"Nicholas","middleName":"S","lastName":"Abend","suffix":""},{"id":492075917,"identity":"8edce783-0d31-4db7-9bdc-5a2b318acb73","order_by":5,"name":"Alicia M Alcamo","email":"","orcid":"","institution":"CHOP: The Children's Hospital of Philadelphia","correspondingAuthor":false,"prefix":"","firstName":"Alicia","middleName":"M","lastName":"Alcamo","suffix":""},{"id":492075918,"identity":"a92e3e08-059f-4662-b842-85c736db077f","order_by":6,"name":"Jimmy W Huh","email":"","orcid":"","institution":"CHOP: The Children's Hospital of Philadelphia","correspondingAuthor":false,"prefix":"","firstName":"Jimmy","middleName":"W","lastName":"Huh","suffix":""},{"id":492075919,"identity":"b2a193dd-decd-47ad-90b9-403f24e7723a","order_by":7,"name":"Shih-shan Chen","email":"","orcid":"","institution":"CHOP: The Children's Hospital of Philadelphia","correspondingAuthor":false,"prefix":"","firstName":"Shih-shan","middleName":"","lastName":"Chen","suffix":""},{"id":492075920,"identity":"92f9d2fa-efcf-42ee-bb68-f52adbac043e","order_by":8,"name":"Robert A Berg","email":"","orcid":"","institution":"CHOP: The Children's Hospital of Philadelphia","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"A","lastName":"Berg","suffix":""},{"id":492075921,"identity":"f5ca062d-0c02-4dbe-89b8-f103ab2ead43","order_by":9,"name":"Alexis A Topjian","email":"","orcid":"","institution":"CHOP: The Children's Hospital of Philadelphia","correspondingAuthor":false,"prefix":"","firstName":"Alexis","middleName":"A","lastName":"Topjian","suffix":""},{"id":492075922,"identity":"1dad6e99-5342-45d5-a7ef-91b779711181","order_by":10,"name":"Craig A Press","email":"","orcid":"","institution":"CHOP: The Children's Hospital of Philadelphia","correspondingAuthor":false,"prefix":"","firstName":"Craig","middleName":"A","lastName":"Press","suffix":""},{"id":492075923,"identity":"6998ca01-c70b-4b8b-bf19-d725ad803131","order_by":11,"name":"Matthew P Kirschen","email":"","orcid":"","institution":"CHOP: The Children's Hospital of Philadelphia","correspondingAuthor":false,"prefix":"","firstName":"Matthew","middleName":"P","lastName":"Kirschen","suffix":""}],"badges":[],"createdAt":"2025-07-24 02:13:51","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7200528/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7200528/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12028-025-02422-x","type":"published","date":"2026-01-08T15:59:21+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":100069448,"identity":"879b8f00-9a7c-45d3-a9eb-6af303353bae","added_by":"auto","created_at":"2026-01-12 16:14:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1135536,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7200528/v1/01ab48f6-41a8-4b87-a962-86338db38223.pdf"},{"id":87938286,"identity":"e020c034-93ad-4a49-af98-9c924645ca1a","added_by":"auto","created_at":"2025-07-30 14:51:37","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":34019,"visible":true,"origin":"","legend":"","description":"","filename":"STROBEchecklistMazzioHTSEEG.docx","url":"https://assets-eu.researchsquare.com/files/rs-7200528/v1/dcdd86c2ad8afee4df03a2ea.docx"}],"financialInterests":"","formattedTitle":"Association of EEG Response to Hypertonic Saline and Neurologic Outcomes in Pediatric Acute Brain Injury","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute brain injury accounts for 15% of pediatric intensive care units (PICUs) admissions and is a leading cause of morbidity and mortality.\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e The acutely injured brain is highly vulnerable to secondary insults such as cerebral edema, elevated intracranial pressure, and impaired cerebral blood flow, all of which can exacerbate injury and worsen outcomes. Patients with acute brain injury frequently undergo continuous electroencephalographic (EEG) monitoring to detect and guide management of subclinical seizures.\u003csup\u003e\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e–\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Additionally, EEG background features are biomarkers of acute brain injury severity. More normal background features such as continuous activity, the presence of faster frequencies, and the presence of variability are associated with favorable neurologic outcomes.\u003csup\u003e\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13 CR14 CR15\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e–\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Further, tracking the trajectory of a patient’s EEG background over the course of an illness can provide insight into the severity of the disease process, response to therapies, and inform prognosis.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eQuantitative EEG (qEEG) allows for objective assessment of EEG background activity by deconstructing raw EEG signals into frequency bands (alpha, beta, theta, and delta) and calculating the power within each frequency band over time. qEEG metrics have been associated with both cerebral injury severity and neurologic outcomes in pediatric populations.\u003csup\u003e\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e–\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e The alpha-delta ratio (ADR), a commonly used qEEG metric in adult neurocritical care, reflects the relative balance of faster (alpha) and slower (delta) frequency components. Cerebral blood flow is one of many factors that modulates ADR; reductions in cerebral blood flow lead to a loss of faster frequencies and a predominance of slower waveforms, yielding a decreased ADR.\u003csup\u003e\u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e–\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e In critically ill adults, ADR is sensitive to clinically apparent ischemic events such as delayed cerebral ischemia following subarachnoid hemorrhage.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan additionalcitationids=\"CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e–\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eHypertonic saline (HTS) is commonly administered to patients to manage intracranial hypertension, potentially improving cerebral blood flow through osmotic shifts, reduction in blood viscosity, and plasma volume expansion.\u003csup\u003e\u003cspan additionalcitationids=\"CR40\" citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e–\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e It is unclear whether changes in ADR are demonstrable after more subtle and transient increases in cerebral blood flow, such as those induced by HTS. Furthermore, it is unknown whether transient increases in ADR have prognostic significance in children with acute brain injury. Thus, in a cohort of children with acute brain injury, we aimed to determine whether administration of clinically indicated 3% HTS was associated with an increase in ADR, and whether there was an association between ADR response to HTS and favorable neurologic outcome. We hypothesized that patients with an ADR response to HTS would have higher rates of survival with favorable neurologic outcome compared to patients without an ADR response. Lastly, we evaluated the relationship between a sustained versus a transient ADR response to HTS and outcome, hypothesizing that patients with a sustained ADR response would have an increased likelihood of survival with a favorable neurologic outcome.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis was a single-center retrospective observational cohort study of patients admitted to the PICU with an acute brain injury who received at least one dose of HTS as part of clinical care while undergoing continuous electroencephalographic (cEEG) monitoring from January 1, 2018, to July 31, 2023. Exclusion criteria included: (1) younger than three months of age, (2) excessive artifact, as determined by an epileptologist, rendering it unsuitable for quantitative analysis, and (3) insufficient EEG data surrounding the analyzed HTS dose. The study was approved by the Children’s Hospital of Philadelphia Institutional Review Board, and a waiver of consent was obtained for this retrospective review of clinically collected data.\u003c/p\u003e\u003cp\u003eWe obtained clinical characteristics, including pre-ICU admission baseline and hospital discharge Functional Status Scale (FSS) scores from a local Virtual Pediatric Systems (VPS) database.\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e We abstracted the timing and dose of hypertonic saline (HTS), along with pre- and post-administration sodium and carbon dioxide (CO₂) values, from the electronic medical record. Pre-HTS values were defined as the sodium and CO₂ measurements obtained within 3 hours prior to HTS administration, selecting the value closest to the time of administration. Post-HTS values were the most proximal measurements within 3 hours after administration. CO₂ levels were preferentially obtained from arterial or venous blood gases. If unavailable, we used hourly recorded end-tidal CO₂ values. For each patient, only the first dose of 3% HTS administered during continuous EEG monitoring was included in the analysis. At our institution, 3% HTS was administered at a standard dose of 2–5 mL/kg, and no other concentrations were used. Patients may have received a dose of HTS prior to cEEG monitoring or had insufficient EEG data surrounding a prior dose for analysis (e.g., EEG disconnected to obtain neuroimaging). Neuroimaging studies were independently reviewed by a pediatric neuroradiologist, and the severity of acute brain injury was categorized as normal (no acute injury), moderate (injury not meeting severe criteria), or severe (presence of midline shift or herniation).\u003c/p\u003e\u003cp\u003ecEEG was performed as part of clinical care using a standard 10–20 electrode montage for all patients (Natus, version 9.3.1 2013). A board certified pediatric electroencephalographer reviewed all raw EEG tracings to ensure the segments surrounding HTS doses were free of artifact that could impact qEEG analysis and that no seizures were present. Additionally, they classified the cEEG background into three categories based on standard definitions: (1) continuous with normal voltage, (2) continuous or nearly continuous with low or normal voltage, and (3) discontinuous, burst-suppression, or suppressed patterns.\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eRaw EEG signals were processed in Persyst (Version 15, Persyst Development Corporation, Prescott, AZ), utilizing artifact reduction and fast Fourier transformation (FFT) analysis to compute power spectral densities estimates. Alpha (8–13 Hz) and delta (1–4 Hz) power were extracted using a running average over 8-second epochs. The ADR for each hemisphere was calculated as the quotient of alpha power divided by delta power. We abstracted the ADR for a total of 40 minutes, extending from 5 minutes prior to the HTS dose to 30 minutes following the 5-minute infusion duration. \u003cem\u003eBaseline ADR\u003c/em\u003e was the average ADR over the 5-minute period before HTS administration. \u003cem\u003ePost-HTS ADR\u003c/em\u003e was calculated as the average ADR during each of the following time intervals: 0–10, 11–20, and 21–30 minutes following HTS administration. ADRs were calculated separately for each hemisphere for all timepoints. An ADR response to HTS was defined as an increase of greater than 20% from baseline in either hemisphere during at least one of the three post-HTS time intervals. The 20% threshold was extrapolated from prior studies using ADR to detect delayed cerebral ischemia in adult subarachnoid hemorrhage, hemispheric differences in stroke, and cerebral blood flow changes during neonatal aortic arch reconstruction.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e–\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e Among patients with an ADR response, the response was categorized as sustained or transient. A \u003cem\u003esustained response\u003c/em\u003e was defined as an ADR increase of \u0026gt; 20% that persisted for at least two consecutive time intervals (totaling at least 20 minutes) or from onset through the end of the 30-minute post-HTS monitoring interval; all other responses were classified as \u003cem\u003etransient responders\u003c/em\u003e.\u003c/p\u003e\u003cp\u003eThe primary outcome was survival with a favorable neurologic outcome, defined as survival with an FSS score change of \u0026lt; 3 from pre-ICU admission to hospital discharge.\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e The secondary outcome was survival to hospital discharge.\u003c/p\u003e\u003cp\u003eWe report descriptive statistics as median and interquartile ranges (IQR) for continuous variables and frequencies with percentages for categorical variables. We used Chi-squared or Fisher exact tests to examine associations between categorical variables and outcome, and Wilcoxon rank-sum to compare continuous variables between exposure and outcome groups. All statistical tests were two-sided, and p \u0026lt; 0.05 was considered statistically significant. Univariable logistic regression was used to assess the association between ADR response and outcome. As a secondary analysis we stratified patients based on EEG background category to assess if the association between ADR response and outcome differed by EEG background. We conducted two sensitivity analyses to exclude patients who (1) received a dose of HTS prior to cEEG initiation, and (2) had acute hypoxic-ischemic brain injury.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAmong 151 patients who met inclusion criteria, 64 were excluded due to age less than 3 months (n=4), excessive EEG artifact (n=7), or insufficient EEG data (n=53). Thus, 87 patients were analyzed. The median age was 10.4 years (IQR 3.6\u0026ndash;14.5), and 46% were female. An ADR response to HTS occurred in 28% of patients (24/87). Compared to ADR non-responders, ADR responders were older (12.9 [10.5-15.0] vs. 8.0 [2.2-12.2] years, \u003cem\u003ep\u003c/em\u003e\u003cem\u003e=\u003c/em\u003e0.004), but the two groups did not differ in other demographics or illness severity metrics (Table 1). ADR responders were more likely to have a continuous and normal voltage EEG background compared to ADR non-responders (67% vs. 40%, \u003cem\u003ep\u003c/em\u003e\u003cem\u003e=\u003c/em\u003e0.01). Median dose of HTS was similar between responders and non-responders (5.0 [4.3-5.0] vs. [4.6 3.0-5.0] mL/kg, p=0.28). Changes in serum sodium and CO\u003csub\u003e2\u003c/sub\u003e levels pre- and post-HTS dose were similar between ADR responder groups (Table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSurvival with a favorable neurologic outcome occurred in 17% of patients (15/87), and survival to hospital discharge occurred in 66% of patients (58/87) (Tables 2 and 3). More ADR responders survived with a favorable neurologic outcome than ADR non-responders (33% vs. 11%, p=0.03). Having an ADR response was associated with 4 times increased odds of favorable neurologic outcome (OR 4.0, 95% CI 1.3\u0026ndash;12.7). Survival to hospital discharge was higher among ADR responders compared to non-responders (83% vs. 60%, p=0.05), corresponding to 3.9 times greater odds of survival (OR 3.9, 95% CI 1.0\u0026ndash;10.7)\u003c/p\u003e\n\u003cp\u003eAmong ADR responders, 25% (6/24) patients demonstrated a response onset within the 0\u0026ndash;10 minute interval, 66% (16/24) during the 11\u0026ndash;20 minute interval, and 8% (2/24) during the 21\u0026ndash;30 minute interval. The ADR response was sustained in 75% (18/24) patients and transient in 25% (6/24) patients. Among patients who survived with a favorable neurologic outcome, a greater proportion had a sustained versus transient ADR response, although the difference was not statistically significant (39% vs. 17%, OR 3.2 [0.3 \u0026ndash; 33.6]).\u003c/p\u003e\n\u003cp\u003eWhen stratified by EEG background category, the association between ADR response and favorable neurologic outcome remained directionally consistent but was not statistically significant across strata (Table 4). In patients with continuous and normal voltage EEG, survival with favorable neurologic outcome occurred in 44% of ADR-responders compared to 28% of ADR non-responders (OR 2.0 [0.5-7.7). No patients with severely abnormal EEG backgrounds survived with favorable neurologic outcome.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eForty-two percent (37/87) of patients received at least one dose of HTS prior to cEEG initiation. When evaluating the 50 patients whose first dose of HTS administrations was captured on cEEG, ADR responders had higher rates of survival with favorable neurologic outcomes than ADR non-responders (38% vs. 8%, \u0026nbsp;OR 7.08 [1.39\u0026ndash;35.99]). When evaluating patients without hypoxic ischemic brain injury (n=63), there was no difference in rates of favorable neurologic outcome (44% vs. 17%, OR 2.5 [0.7\u0026ndash;8.4]) or survival to hospital discharge (90% vs. 71%, OR 3.8 [0.76\u0026ndash;18.9) among ADR responders and ADR non-responders.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn a cohort of critically ill children with acute brain injury, patients with a \u0026gt;20% increase in ADR within 30 mins of HTS administration had four times the odds of survival with a favorable neurologic outcome compared to ADR non-responders. The association between an ADR response and favorable neurologic outcome was strongest among patients with more normal EEG backgrounds (continuous and normal voltage), highlighting a subgroup with likely less severe injury in whom a response to HTS may more readily translate into clinical benefit. most clinically relevant. An increase in faster EEG frequencies (alpha) or a reduction in slower frequencies (delta) following HTS administration likely reflects improved cerebral blood flow in salvageable brain tissue.\u0026nbsp;\u003csup\u003e21,26\u0026ndash;28\u003c/sup\u003e Thus, an ADR response to HTS may potentially serve as a noninvasive biomarker of neurovascular responsiveness in acute brain injury, identifying patients with the potential to benefit from strategies that improve cerebral blood flow.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eADR can be calculated automatically in real-time and displayed continuously at the bedside, allowing clinicians to evaluate EEG changes in response to interventions aimed at improving cerebral physiology. The qEEG response, or lack of response, to an intervention may provide information about the physiologic state of the brain that can guide subsequent neuroprotective therapies. For example, the presence of an ADR response to HTS may suggest further therapies aimed at improving cerebral blood flow could be beneficial. On the other hand, the absence of an ADR response may identify children with less severe brain injury and intact cerebral autoregulation, children for whom a single dose of HTS is insufficient and more aggressive ICP management is needed, or children with severe irreversible brain injury unlikely to benefit from therapies aimed at increasing cerebral perfusion. While qEEG and serial ADR monitoring are commonly used in adult neurocritical care and have demonstrated high sensitivity (83\u0026ndash;100%) and specificity (74\u0026ndash;84%) for detecting delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage,\u003csup\u003e29,35,37\u003c/sup\u003e, it is an emerging tool for neuromonitoring in pediatric populations.\u003csup\u003e20,22,27,30,31\u003c/sup\u003e For example, in neonates undergoing congenital heart surgery, the development of an interhemispheric alpha-delta ratio (ADR) difference greater than 25% has been associated with subsequent neurologic injury.\u003csup\u003e27,28\u003c/sup\u003e Our findings build on prior work by demonstrating the value of a detectable, real-time qEEG response to a physiologic intervention.\u003c/p\u003e\n\u003cp\u003eIdentifying patients with an ADR response following HTS may help understand the cerebral physiological and likelihood of clinical benefit from additional hyperosmolar therapy. There is mixed evidence and large practice variation in the use of HTS in patients with primarily cytotoxic cerebral edema from etiologies such as hypoxic ischemic brain injury from cardiac arrest, infectious encephalitis, and ischemic strokes. The use of HTS in hypoxic ischemia brain injury decreases brain edema in animal models but has failed to show improvement in clinical studies.\u003csup\u003e45,46\u003c/sup\u003e However, recent work suggests that in hypoxic ischemic brain injury, HTS may reduce perivascular edema and thereby improve oxygen diffusion into brain tissue.\u003csup\u003e47\u003c/sup\u003e In our cohort, only one of the 24 patients with hypoxic ischemic brain injury achieved a favorable outcome, and this patient was an ADR responder. In this context, an EEG-based marker like ADR responsiveness may offer a physiologic tool to differentiate patients likely to benefit from HTS from those who may require alternative neuroprotective management strategies.\u003c/p\u003e\n\u003cp\u003eEEG background following pediatric acute brain injury is a strong predictor of outcome.\u003csup\u003e5,9\u0026ndash;11,48\u003c/sup\u003e In our study, nearly all children who survived with favorable neurologic outcome exhibited continuous and normal voltage EEG backgrounds. Although not statistically significant, the presence of an ADR response appeared to further stratify patients with continuous EEG backgrounds, with double the percentage of patients experiencing favorable outcomes who had both a continuous EEG background and an ADR response to HTS compared to patients with a continuous EEG background who did not have an ADR response to HTS. These findings warrant further investigation in larger cohorts. Among patients with continuous, normal-voltage EEGs who did not demonstrate an ADR response, it is possible that some had relatively mild injuries with preserved cerebral autoregulation such that HTS did not produce a sufficient increase in cerebral blood flow to elicit detectable EEG changes. Others may have received HTS in the setting of a clinical concern despite the patient not having intracranial hypertension, in which case a marked change in cerebral blood flow would not be expected. Notably, only one patient with a severely abnormal EEG background in our cohort exhibited an ADR response, and this patient did not survive to hospital discharge. Taken together, these findings suggest that ADR response should not be used in isolation to predict neurologic outcome and that larger studies are needed to better define the relationship between ADR response and EEG background features.\u003c/p\u003e\n\u003cp\u003eOur study has several limitations. The retrospective, single‑center design and modest sample size limited our ability to perform multivariable regression analyses. Our cohort was comprised of patients who received HTS doses while on EEG, often using a patient\u0026rsquo;s second or third dose for analyses, potentially underestimating the observed association, as the efficacy of HTS may wane with repeated doses. As this was a retrospective observational study, we could not account for the effect a prior HTS response had on the clinician\u0026rsquo;s decisions to give additional HTS. EEG background categorization was based on a five-minute epoch immediately preceding HTS administration. While this short interval was chosen to capture the acute cerebral physiology at the time clinicians made the decision to give HTS, it risks potential misclassification of a patient\u0026rsquo;s true baseline ADR that may have been more evident if a longer baseline interval was used. We did not have concurrent intracranial pressure data to determine whether HTS-associated ADR changes were associated with a decrease in intracranial pressure or an increase in cerebral perfusion pressure. Finally, the 20% ADR threshold was extrapolated from prior studies of cerebral ischemia in adults and children, but prospective studies are needed to determine optimal cut‑points in children.\u0026nbsp;\u003csup\u003e28,29,32,34\u0026ndash;36,38\u003c/sup\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eA greater than 20% increase in ADR within 30 minutes of HTS administration was associated with increased survival with favorable neurologic outcome in critically ill children with acute brain injury. Quantitative EEG response to physiologic-targeted interventions is a promising noninvasive tool to aid in both prognostication and therapeutic decision-making in pediatric acute brain injury.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eWe confirm that this manuscript complies with all author instructions provided.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEmma L. Mazzio MD: Conceptualization, Methodology, Investigation, Formal analysis, Writing - original draft, Writing - review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eEva Catenaccio MD: Conceptualization, Methodology, Investigation, Writing - review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eRaymond Liu MD: Conceptualization, Investigation, Formal analysis, Writing - review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eArastoo Vossough MD PhD: Investigation, Writing - review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eNicholas S. Abend MD MSCE: Conceptualization, Investigation, Writing - review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eAlicia M Alcamo MD MPH: Conceptualization, Writing - review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eJimmy Huh MD: Conceptualization, Writing - review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eShih-shan Chen MD: Conceptualization, Writing - review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eRobert A Berg MD: Conceptualization, Methodology, Investigation, Writing - review \u0026amp; editing, Supervision\u003c/p\u003e\n\u003cp\u003eAlexis A Topjian MD MSCE: Methodology, Formal analysis, Writing - original draft, Writing- review \u0026amp; editing, Supervision\u003c/p\u003e\n\u003cp\u003eCraig Press MD PhD: \u0026nbsp;Conceptualization, Investigation, Methodology, Writing - review \u0026amp; editing, Supervision\u003c/p\u003e\n\u003cp\u003eMatthew P Kirschen MD PhD: Conceptualization, Methodology, Formal analysis, Writing - review \u0026amp; editing, Supervision\u003c/p\u003e\n\u003cp\u003eWe confirm that all authorship requirements have been met and the final manuscript has been approved by all authors.\u003c/p\u003e\n\u003cp\u003eThis manuscript has not been published elsewhere and is not under consideration by another journal.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Children\u0026rsquo;s Hospital of Philadelphia Institutional Review Board, and waiver of consent was obtained for this retrospective review of clinically collected data.\u003c/p\u003e\n\u003cp\u003eA.A.T. receives NIH funding to her institution and serves as an Associate Editor for Resuscitation (Elsevier). A.M.A. receives research funding from Edwards Lifesciences for work unrelated to this project. M.P.K. receives NIH funding to his institution (NINDS K23NS116120). Persyst provided a complimentary research license (version 15) for this project. No other authors have conflicts of interest to disclose.\u003c/p\u003e\n\u003cp\u003eWe used the Strobe reporting checklist, attached.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNo funding sources for this study.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAu AK, Carcillo JA, Clark RSB, Bell MJ. Brain injuries and neurological system failure are the most common proximate causes of death in children admitted to a pediatric intensive care unit. \u003cem\u003ePediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc\u003c/em\u003e. 2011;12(5):566-571. doi:10.1097/PCC.0b013e3181fe3420\u003c/li\u003e\n\u003cli\u003eMoreau JF, Fink EL, Hartman ME, et al. 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Correlation of Regional Cerebral Blood Flow (rCBF) with EEG Changes During Isoflurane Anesthesia for Carotid Endarterectomy. \u003cem\u003eAnesthesiology\u003c/em\u003e. 1987;66:344-349. doi:10.1097/00000542-198703000-00014\u003c/li\u003e\n\u003cli\u003eLansinger J, Swartz MF, Scheffler EJ, et al. Quantitative Electroencephalography Alpha:Delta Ratio and Suppression Ratio Monitoring During Infant Aortic Arch Reconstruction. \u003cem\u003ePediatr Neurol\u003c/em\u003e. 2025;163:96-103. doi:10.1016/j.pediatrneurol.2024.12.002\u003c/li\u003e\n\u003cli\u003eSwartz MF, Lansinger J, Scheffler EJ, et al. Changes in Neonatal Intraoperative Electroencephalogram Alpha: Delta Ratios Precede Neurologic Injury. \u003cem\u003eWorld J Pediatr Congenit Heart Surg\u003c/em\u003e. 2025;16(1):21-29. doi:10.1177/21501351241269963\u003c/li\u003e\n\u003cli\u003eYu Z, Wen D, Zheng J, et al. Predictive Accuracy of Alpha-Delta Ratio on Quantitative Electroencephalography for Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage: Meta-Analysis. \u003cem\u003eWorld Neurosurg\u003c/em\u003e. 2019;126:e510-e516. doi:10.1016/j.wneu.2019.02.082\u003c/li\u003e\n\u003cli\u003eAppavu BL, Temkit MH, Foldes ST, et al. Quantitative Electroencephalography After Pediatric Anterior Circulation Stroke. \u003cem\u003eJ Clin Neurophysiol\u003c/em\u003e. 2022;39(7):610. doi:10.1097/WNP.0000000000000813\u003c/li\u003e\n\u003cli\u003eMunjal NK, Bergman I, Scheuer ML, Genovese CR, Simon DW, Patterson CM. Quantitative Electroencephalography (EEG) Predicting Acute Neurologic Deterioration in the Pediatric Intensive Care Unit: A Case Series. \u003cem\u003eJ Child Neurol\u003c/em\u003e. 2022;37(1):73-79. doi:10.1177/08830738211053908\u003c/li\u003e\n\u003cli\u003eGollwitzer S, Groemer T, Rampp S, et al. Early prediction of delayed cerebral ischemia in subarachnoid hemorrhage based on quantitative EEG: A prospective study in adults. \u003cem\u003eClin Neurophysiol\u003c/em\u003e. 2015;126(8):1514-1523. doi:10.1016/j.clinph.2014.10.215\u003c/li\u003e\n\u003cli\u003eGaspard N. Current Clinical Evidence Supporting the Use of Continuous EEG Monitoring for Delayed Cerebral Ischemia Detection: \u003cem\u003eJ Clin Neurophysiol\u003c/em\u003e. 2016;33(3):211-216. doi:10.1097/WNP.0000000000000279\u003c/li\u003e\n\u003cli\u003eRots ML, van Putten MJAM, Hoedemaekers CWE, Horn J. Continuous EEG Monitoring for Early Detection of Delayed Cerebral Ischemia in Subarachnoid Hemorrhage: A Pilot Study. \u003cem\u003eNeurocrit Care\u003c/em\u003e. 2016;24(2):207-216. doi:10.1007/s12028-015-0205-y\u003c/li\u003e\n\u003cli\u003eClaassen J, Hirsch LJ, Kreiter KT, et al. Quantitative continuous EEG for detecting delayed cerebral ischemia in patients with poor-grade subarachnoid hemorrhage. \u003cem\u003eClin Neurophysiol\u003c/em\u003e. 2004;115(12):2699-2710. doi:10.1016/j.clinph.2004.06.017\u003c/li\u003e\n\u003cli\u003eWickering E, Gaspard N, Zafar S, et al. Automation of Classical QEEG Trending Methods for Early Detection of Delayed Cerebral Ischemia: More Work to Do. \u003cem\u003eJ Clin Neurophysiol\u003c/em\u003e. 2016;33(3):227. doi:10.1097/WNP.0000000000000278\u003c/li\u003e\n\u003cli\u003eScherschinski L, Catapano JS, Karahalios K, et al. Electroencephalography for detection of vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a retrospective analysis and systematic review. Published online March 1, 2022. doi:10.3171/2021.12.FOCUS21656\u003c/li\u003e\n\u003cli\u003eKamitaki BK, Tu B, Wong S, Mendiratta A, Choi H. Quantitative EEG Changes Correlate With Post-Clamp Ischemia During Carotid Endarterectomy. \u003cem\u003eJ Clin Neurophysiol\u003c/em\u003e. 2021;38(3):213-220. doi:10.1097/WNP.0000000000000686\u003c/li\u003e\n\u003cli\u003eQureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. \u003cem\u003eCrit Care Med\u003c/em\u003e. 2000;28(9):3301-3313. doi:10.1097/00003246-200009000-00032\u003c/li\u003e\n\u003cli\u003eSuarez JI. Hypertonic saline for cerebral edema and elevated intracranial pressure. \u003cem\u003eCleve Clin J Med\u003c/em\u003e. 2004;71 Suppl 1:S9-13. doi:10.3949/ccjm.71.suppl_1.s9\u003c/li\u003e\n\u003cli\u003eTseng MY, Al-Rawi PG, Pickard JD, Rasulo FA, Kirkpatrick PJ. Effect of hypertonic saline on cerebral blood flow in poor-grade patients with subarachnoid hemorrhage. \u003cem\u003eStroke\u003c/em\u003e. 2003;34(6):1389-1396. doi:10.1161/01.STR.0000071526.45277.44\u003c/li\u003e\n\u003cli\u003eVirtual Pediatric Systems | Online. Accessed June 18, 2025. https://myvps.org/\u003c/li\u003e\n\u003cli\u003eHirsch LJ, Fong MWK, Leitinger M, et al. American Clinical Neurophysiology Society\u0026rsquo;s Standardized Critical Care EEG Terminology: 2021 Version. \u003cem\u003eJ Clin Neurophysiol\u003c/em\u003e. 2021;38(1):1-29. doi:10.1097/WNP.0000000000000806\u003c/li\u003e\n\u003cli\u003ePollack MM, Holubkov R, Glass P, et al. Functional Status Scale: new pediatric outcome measure. \u003cem\u003ePediatrics\u003c/em\u003e. 2009;124(1):e18-28. doi:10.1542/peds.2008-1987\u003c/li\u003e\n\u003cli\u003eFuller ZL, Faro JW, Callaway CW, Coppler PJ, Elmer J. Recovery among post-arrest patients with mild-to-moderate cerebral edema. \u003cem\u003eResuscitation\u003c/em\u003e. 2021;162:149-153. doi:10.1016/j.resuscitation.2021.02.033\u003c/li\u003e\n\u003cli\u003eMarasini S, Jia X. Neuroprotective Approaches for Brain Injury After Cardiac Arrest: Current Trends and Prospective Avenues. \u003cem\u003eJ Stroke\u003c/em\u003e. 2024;26(2):203-230. doi:10.5853/jos.2023.04329\u003c/li\u003e\n\u003cli\u003eHoiland RL, Ainslie PN, Wellington CL, et al. Brain Hypoxia Is Associated With Neuroglial Injury in Humans Post-Cardiac Arrest. \u003cem\u003eCirc Res\u003c/em\u003e. 2021;129(5):583-597. doi:10.1161/CIRCRESAHA.121.319157\u003c/li\u003e\n\u003cli\u003eAdmiraal MM, Horn J, Hofmeijer J, et al. EEG reactivity testing for prediction of good outcome in patients after cardiac arrest. \u003cem\u003eNeurology\u003c/em\u003e. 2020;95(6):e653-e661. doi:10.1212/WNL.0000000000009991\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Patient Demographic and Clinical Characteristics by ADR Response to Hypertonic Saline\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"768\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 270px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll Patients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=87)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eADR Responder (n=24)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eADR Non-Responder (n=63)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years) (median [IQR])\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e10.4 [3.6-14.5]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e12.9 [10.6-15.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e8.0 [2.2-12.2]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e40 (46%)\u003c/p\u003e\n \u003cp\u003e47 \u0026nbsp;(54%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e15 (63%)\u003c/p\u003e\n \u003cp\u003e9 \u0026nbsp;(38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e25 (40%)\u003c/p\u003e\n \u003cp\u003e38 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre-ICU FSS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e6 [6-6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e6 [6-6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e6 [6-6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePRISM3 Score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e11 [5-17]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e11 [5-15]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e11 [6-18]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreviously healthy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e57 (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e18 (75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e39 (62%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEtiology of Acute Brain Injury\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Anoxic\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Trauma \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;ICH non-traumatic\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Neuroinflammatory/infectious\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Metabolic\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Ischemic stroke\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Status epilepticus\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e24 (28%)\u003c/p\u003e\n \u003cp\u003e24 (28%)\u003c/p\u003e\n \u003cp\u003e15 (17%)\u003c/p\u003e\n \u003cp\u003e12 (14%)\u003c/p\u003e\n \u003cp\u003e4 (6%)\u003c/p\u003e\n \u003cp\u003e4 (6%)\u003c/p\u003e\n \u003cp\u003e2 (2%)\u003c/p\u003e\n \u003cp\u003e2 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (13%)\u003c/p\u003e\n \u003cp\u003e9 (38%)\u003c/p\u003e\n \u003cp\u003e5 (38%)\u003c/p\u003e\n \u003cp\u003e3 (13%)\u003c/p\u003e\n \u003cp\u003e2 (8%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003cp\u003e2 (8%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21 (33%)\u003c/p\u003e\n \u003cp\u003e15 (24%)\u003c/p\u003e\n \u003cp\u003e10 (16%)\u003c/p\u003e\n \u003cp\u003e9 (14%)\u003c/p\u003e\n \u003cp\u003e2 (3%)\u003c/p\u003e\n \u003cp\u003e4 (6%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003cp\u003e2 (3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEEG background category\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eCont, normal voltage\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Cont./nearly cont. +/- low voltage\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Discont./ Suppressed/ Burst-suppression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e41 (47%)\u003c/p\u003e\n \u003cp\u003e23 (26%)\u003c/p\u003e\n \u003cp\u003e23 (26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16 (67%)\u003c/p\u003e\n \u003cp\u003e7 (29%)\u003c/p\u003e\n \u003cp\u003e1 (4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25 (40%)\u003c/p\u003e\n \u003cp\u003e32 (51%)\u003c/p\u003e\n \u003cp\u003e6 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeuroimaging severity (n=81)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eNormal\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Mild to Moderate\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Severe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9 (10%)\u003c/p\u003e\n \u003cp\u003e46 (53%)\u003c/p\u003e\n \u003cp\u003e25 (29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (8%)\u003c/p\u003e\n \u003cp\u003e17 (71%)\u003c/p\u003e\n \u003cp\u003e5 (21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (11%)\u003c/p\u003e\n \u003cp\u003e30 (46%)\u003c/p\u003e\n \u003cp\u003e20 (32%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDose of HTS (ml/kg)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e4.8 [3.1-5.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e5.0 [4.3-5.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e4.6 [3.0-5.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre-HTS Sodium (n= 85)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e∆ Sodium (n = 84)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePre-HTS CO2 (n= 85)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e∆ CO2 (n = 85)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e139 [135-145]\u003c/p\u003e\n \u003cp\u003e2 [1-4]\u003c/p\u003e\n \u003cp\u003e36 \u0026nbsp;[33-39]\u003c/p\u003e\n \u003cp\u003e0 [-2 -2]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e142 [139-145]\u003c/p\u003e\n \u003cp\u003e2 [1-4]\u003c/p\u003e\n \u003cp\u003e35 [31-38]\u003c/p\u003e\n \u003cp\u003e1 [-3-2]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e138 [134-145]\u003c/p\u003e\n \u003cp\u003e2 [1-4]\u003c/p\u003e\n \u003cp\u003e36 [33-40]\u003c/p\u003e\n \u003cp\u003e0 [-2-2]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;FSS = Functional Status Score, PRISM3 = Pediatric risk of Mortality Score 3, Cont. = continuous, Discont. = discontinuous, ICH = intracranial hemorrhage, HTS= hypertonic saline,\u0026nbsp;\u003c/em\u003e\u003cem\u003e∆ Sodium = Pre/post HTS change, CO2 = carbon dioxide level from blood gas,\u0026nbsp;\u003c/em\u003e\u003cem\u003e∆ CO2 = Pre/post HTS change in CO2 from blood gas or EtCO2.\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Association Between ADR Response to HTS and Favorable Neurologic Outcome\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"714\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll Patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=87)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eADR Responder\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=24)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eADR Non-Responder\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=63)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOdds Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFavorable Neurologic Outcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e15 (17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e8 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e7 (11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e4.0 (1.3-12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurvival\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e58 (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e20 (83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e38 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e3.9 (1.0-10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2: \u003cem\u003eAssociation between ADR response and favorable neurologic outcome and survival to hospital discharge. (ADR = alpha-delta ratio)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3:\u0026nbsp;\u003c/strong\u003ePatient Demographic and Clinical Characteristics by Primary Outcome\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"726\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 285px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFavorable Neuro Outcome\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=15)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-Favorable Neuro Outcome\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=72)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 285px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years) (median [IQR])\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 179px;\"\u003e\n \u003cp\u003e10.4 [6.9-13.9]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e10.4 [2.8-14.5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 285px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 179px;\"\u003e\n \u003cp\u003e9 (60%)\u003c/p\u003e\n \u003cp\u003e6 \u0026nbsp; \u0026nbsp; (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e31 (43%)\u003c/p\u003e\n \u003cp\u003e41 (57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 285px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline FSS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 179px;\"\u003e\n \u003cp\u003e6 [6-6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e6 [6-6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 285px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePRISM3 Score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 179px;\"\u003e\n \u003cp\u003e5 [5-15]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e13 [8-18]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 285px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreviously healthy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 179px;\"\u003e\n \u003cp\u003e8 (53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e49 (68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 285px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEtiology of Acute Brain Injury\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Hypoxic Ischemic\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Trauma \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;ICH non-traumatic\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Neuroinflammatory/infectious\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Metabolic\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Ischemic stroke\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Status epilepticus\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Other\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (7%)\u003c/p\u003e\n \u003cp\u003e2 (13%)\u003c/p\u003e\n \u003cp\u003e4 (27%)\u003c/p\u003e\n \u003cp\u003e4 (27%)\u003c/p\u003e\n \u003cp\u003e3 (20%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003cp\u003e1 (7%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23 (32%)\u003c/p\u003e\n \u003cp\u003e22 (30%)\u003c/p\u003e\n \u003cp\u003e11 (15%)\u003c/p\u003e\n \u003cp\u003e8 (11%)\u003c/p\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003cp\u003e4 (6%)\u003c/p\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003cp\u003e2 (3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 285px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEEG background category\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eCont. normal voltage\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Cont./nearly cont. +/- low voltage\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Discont./suppressed/ Burst-suppression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (93%)\u003c/p\u003e\n \u003cp\u003e1 (7%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27 (38%)\u003c/p\u003e\n \u003cp\u003e22 (31%)\u003c/p\u003e\n \u003cp\u003e23 (32%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 285px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeuroimaging severity\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Normal\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Mild to Moderate\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Severe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (20%)\u003c/p\u003e\n \u003cp\u003e10 (67%)\u003c/p\u003e\n \u003cp\u003e2 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (8%)\u003c/p\u003e\n \u003cp\u003e37 (51%)\u003c/p\u003e\n \u003cp\u003e23 (32%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;FSS = Functional Status Score, PRISM3 = Pediatric risk of Mortality Score 3, Cont. = continuous, Discont. = discontinuous, ICH = intracranial hemorrhage, HTS= hypertonic saline.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4: Association Between ADR Response to HTS and Outcome, Stratified by EEG Background\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"734\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 734px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eContinuous, Normal Voltage Background EEG\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll (n=41)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eADR Responder (n =16)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eADR Non-Responder (n=25)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFavorable Neurologic Outcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e14 (34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e7 (44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e7 (28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e2.0 [0.5-7.7]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurvival\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e35 (85%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e15 (93%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e20 (80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e3.3 [0.4- 94.8]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 734px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eContinuous or Nearly Continuous +/- Low Voltage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll (n=23)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eADR Responder (n=7)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eADR Non-Responder (n=16)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFavorable Neurologic Outcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e1 (4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e1 (14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurvival\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e15 (65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e5 (71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e10 (62%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e1.4 [0.21- 13.98]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 734px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiscontinuous, Suppressed, Burst suppressed\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll (n=23)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eADR Responder (n=1)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eADR Non-Responder (n=22)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFavorable Neurologic Outcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurvival\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e8 (34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 4: \u003cem\u003eComparison of favorable neurologic outcome and survival to hospital discharge among patients with and without an ADR response to hypertonic saline, stratified by EEG background category. (ADR = alpha-delta ratio; EEG = electroencephalography)\u003c/em\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"neurocritical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neca","sideBox":"Learn more about [Neurocritical Care](http://link.springer.com/journal/12028)","snPcode":"12028","submissionUrl":"https://www.editorialmanager.com/neca/default2.aspx","title":"Neurocritical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Pediatrics, Brain Injuries, Critical Care, Quantitative EEG, Cerebral Blood Flow, Hypertonic Saline, Prognosis","lastPublishedDoi":"10.21203/rs.3.rs-7200528/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7200528/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eEEG is a critical tool for neuromonitoring and neuroprognostication in children with acute brain injury. Quantitative EEG (qEEG), particularly the alpha-delta ratio (ADR), can detect worsening cerebral ischemia in adults, but it is unknown whether it can identify more subtle and transient changes in cerebral blood flow, such as those induced by hypertonic saline (HTS), in children. We aimed to determine whether we could identify a cohort of patients with an ADR response to HTS and to evaluate the association between an ADR response and neurologic outcomes in critically ill children with acute brain injury.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003e We conducted a retrospective cohort study of patients admitted to a pediatric intensive care unit with acute brain injury who received HTS during EEG monitoring from 2018\u0026ndash;2023. The ADR was calculated before and after HTS administration. An ADR response was defined as \u0026gt;\u0026thinsp;20% increase from baseline within 30 minutes of receiving HTS in either hemisphere. The primary outcome was survival with favorable neurologic outcome, defined as a Functional Status Scale (FSS) change\u0026thinsp;\u0026lt;\u0026thinsp;3 from pre-hospital baseline to discharge. Secondary outcome was survival to hospital discharge.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAmong 87 patients (median age 10 years [IQR 3.6\u0026ndash;14.5], 46% female), 28% (24/87) had an ADR response to HTS. ADR responders were older (12.9 vs. 8.0 years, p\u0026thinsp;=\u0026thinsp;0.004) and more likely to have continuous, normal-voltage EEG backgrounds (67% vs. 40%, p\u0026thinsp;=\u0026thinsp;0.006). Patients with an ADR response had 4 times increased odds of favorable outcome and survival (OR 4.0, 95% CI 1.3\u0026ndash;12.7; OR 3.9, 95% CI 1.0\u0026ndash;10.7, respectively).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eAn ADR increase\u0026thinsp;\u0026gt;\u0026thinsp;20% following HTS was associated with increased odds of survival with favorable neurologic outcome and survival to hospital discharge in critically ill pediatric patients with acute brain injury. qEEG response to HTS may serve as a real-time, noninvasive biomarker of cerebral perfusion responsiveness.\u003c/p\u003e","manuscriptTitle":"Association of EEG Response to Hypertonic Saline and Neurologic Outcomes in Pediatric Acute Brain Injury","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-30 14:51:32","doi":"10.21203/rs.3.rs-7200528/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-07-28T15:22:24+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-28T14:57:53+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Neurocritical Care","date":"2025-07-28T13:49:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-25T13:18:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"Neurocritical Care","date":"2025-07-24T21:57:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"neurocritical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neca","sideBox":"Learn more about [Neurocritical Care](http://link.springer.com/journal/12028)","snPcode":"12028","submissionUrl":"https://www.editorialmanager.com/neca/default2.aspx","title":"Neurocritical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"0cce2dc2-e22d-4312-bbde-6c70a66e5d4a","owner":[],"postedDate":"July 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-12T16:06:40+00:00","versionOfRecord":{"articleIdentity":"rs-7200528","link":"https://doi.org/10.1007/s12028-025-02422-x","journal":{"identity":"neurocritical-care","isVorOnly":false,"title":"Neurocritical Care"},"publishedOn":"2026-01-08 15:59:21","publishedOnDateReadable":"January 8th, 2026"},"versionCreatedAt":"2025-07-30 14:51:32","video":"","vorDoi":"10.1007/s12028-025-02422-x","vorDoiUrl":"https://doi.org/10.1007/s12028-025-02422-x","workflowStages":[]},"version":"v1","identity":"rs-7200528","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7200528","identity":"rs-7200528","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}